Objective: Vascular endothelial growth factor (VEGF)is involved both in regulation of hyperglycemia and structural modifications in diabetes.VEGF over expression has been observed in muscle cells as a result of hyperglycemia.Furthermore,most of the factors that stimulate the VEGF expression have an important role in diabetes,including hypoxia,high glucose concentration,PKC activation and oxidative stress.Also,VEGF has a role in accelerating diabetic late complications as retinopathy,nephropathy,neuropathy and diabetic foot ulcer (DFU).In this study we have performed a candidate gene association study in order to examine VEGF gene polymorphism association with DFU. Materials and Methods: 5cc of peripheral blood were collected in EDTA tubes from healthy controls and patients with type2 diabetes with and without DFU attending diabetes clinic.Then DNA was extracted from WBCs.Using salting-out method and ARMS-PCR was performed to determine allele and genotype frequencies for VEGF -7*C/T and -2578*C/A polymorphism. Results: The frequency of genotype AA was significantly decreased in patients with DFU compared with diabetic subjects without DFU (AA vs CA+CC, p=0.003, OR=0.44, 95%CI=0.24-0.80), conferring a protective effect. Also there was a significant decrease in frequency of A allele in patients with DFU compared to the controls (p=0.02, OR=0.68, 95%CI=0.48-0.96).There was no significant difference for allele and genotype frequencies of -7*C/T polymorphism between patients and controls. Conclusion: It seems that lower frequency of A allele in patients with DFU is conferring a protective effect which might be as a result of increased angiogenesis in patients carrying this allele.